Project Summary The goal of this proposal is to elucidate neurobehavioral mechanisms of parent-child extinction learning in early adolescent PTSD. Notably, deficits in directly learned fear extinction are implicated in adult PTSD. However, youth with PTSD live within the family system, which could impact their ability to extinguish trauma memories. Indeed, abnormal parent-child transmission of fear following trauma is a potent risk factor for youth PTSD. Furthermore, trauma-focused cognitive behavioral therapy (TF-CBT), the gold-standard treatment for pediatric PTSD, uses exposure therapy of the child's trauma narrative for both youth and their caregiver. Here, TF-CBT aims to promote extinction of trauma-related fear both directly in the child and vicariously through parent modeling. However, no reported studies have examined the cumulative impact of direct and vicarious fear extinction in pediatric PTSD. Finally, the diagnosis of PTSD in youth continues to rely on DSM syndromal criteria, creating a great need to establish objective, biologically based diagnoses. This innovative research program will (1) identify physiological impairments in direct/vicarious fear extinction and their unique contributions to adolescent PTSD, (2) identify the neural substrates of fear acquisition and direct/vicarious extinction learning in adolescent PTSD, and (3) use machine learning on biomarkers of fear acquisition and direct/vicarious extinction to classify trauma exposure and PTSD diagnosis in adolescents. This interdisciplinary research team will recruit 40 non-traumatized typically developing (TD) youth, 40 trauma- exposed comparison (TEC) youth without mental illness, and 80 medication-free youth with PTSD, ages 10-14, along with their primary caregiving parent. Youth and parents will undergo fear acquisition followed by a novel fear extinction paradigm. Here, youth will undergo two extinction training conditions: 1) direct extinction and 2) vicarious extinction by observing their parent complete extinction training. Parent/child skin conductance and corrugator EMG will be measured during all fear protocol phases. Additionally, youth will complete all fear phases during fMRI to probe neural substrates of fear acquisition, and direct and vicarious extinction. Following physiological and fMRI analyses, a deep evolutionary machine learning approach will be applied to youth neurophysiological fear indices to classify trauma and PTSD status. Primary analyses will 1) examine physiological markers of direct and vicarious extinction in youth and their relative contribution to PTSD, 2) examine neural abnormalities during direct and vicarious extinction in adolescent PTSD, and 3) determine whether adding vicarious extinction markers enhances machine learning classification of youth trauma and PTSD status. This ambitious program of parent-child extinction learning promises to yield the first comprehensive set of neurophysiological markers of pediatric PTSD that will allow for objective, rational targeting of treatment in the parent-child dyad to improve outcomes for afflicted youth.